Benign pancreatic hyperenzymemia or Gullo's syndrome.

Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by an abnormal increase in serum pancreatic enzymes in the absence of pancreatic disease. The hyperenzymemia can occur sporadically or in a familial form, and all of the pancreatic enzymes show elevations. Although the condition is persistent, the enzyme elevations fluctuate considerably, even temporarily returning to normal levels at times. In this review the main characteristics of this syndrome are described.

Alcoholic pancreatitis: new pathogenetic insights.

Though amply described, alcoholic pancreatitis continues to stir controversy. One of the most debated points is whether it is a chronic disease since onset or progresses to a chronic form after repeated episodes of acute pancreatitis. Histologic studies on patients with pancreatitis have clearly shown that it is chronic since onset and that if necrotic acute pancreatitis develops in an alcoholic, it occurs in a pancreas damaged by chronic lesions. While the possibility cannot be wholly excluded that alcohol-related acute pancreatitis may develop in the absence of chronic lesions, such an occurrence would be rare. In addition to alcoholism, genetic factors play a determinant role in the pathogenesis of the disease. Genetic studies have suggested that in hereditary pancreatitis mutation of the cationic trypsinogen gene and serine peptidase inhibitor, Kazal type 1 (SPINK1) genes mutations of the may have pathogenetic importance; however, studies on alcoholic pancreatitis have produced disappointing results so far.

Benign pancreatic hyperenzymemia.

Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by an abnormal increase in serum pancreatic enzymes in the absence of pancreatic disease. The hyperenzymemia can occur sporadically or in a familial form, and all of the pancreatic enzymes show elevations. Although the condition is persistent, the enzyme elevations fluctuate considerably, even temporarily returning to normal levels at times. In this review the main characteristics of this syndrome are described.

The quality of life in patients with chronic pancreatitis evaluated using the SF-12 questionnaire: a comparative study with the SF-36 questionnaire.

BACKGROUND: In clinical practice there is the need to utilise a time saving questionnaire to assess the quality of life. AIMS: To establish the validity of the SF-12 questionnaire in chronic pancreatitis patients and to identify the predictors capable of modifying the physical and mental summaries in these patients. QUESTIONNAIRES: SF-12 and SF-36 questionnaires were used. SUBJECTS: One hundred and forty-one outpatients with proven chronic pancreatitis. The data of 141 sex- and age-matched Italian subjects of two normative groups (61,434 Italian subjects for SF-12 and 2031 Italian subjects for SF-36) were used as controls. RESULTS: Chronic pancreatitis patients had the SF-12 physical and mental component summaries significantly related to the SF-36 physical and mental component summaries (P<0.001). The presence of pancreatic pain and non-pancreatic surgery accounted for 41.3% in the formation of the PCS-36 score and 37.2% in that of the PCS-12 score, respectively. Gender, BMI and pancreatic pain accounted for 15.3% of the information in the formation of the MCS-36 and for 14.7% in that of the MCS-12; using these clinical variables, the loss of information in applying the SF-12 instead of the SF-36 was very low (4.1 and 0.6% for the PCS and the MCS, respectively). CONCLUSIONS: The SF-12 is a good alternative to the SF-36 in assessing the quality of life in chronic pancreatitis.

Quality of life in patients with chronic pancreatitis.

INTRODUCTION: Health-related quality of life is becoming a major issue in the evaluation of any therapeutic intervention in patients with chronic or hard to cure diseases. AIMS: To assess the quality of life in patients with chronic pancreatitis, the majority of whom have had the disease for a long time, and to evaluate which factors linked to the disease are able to influence the quality of life. SUBJECTS AND METHODS: A total of 190 consecutive patients (157 males, 33 females; mean age 58.6+/-12.7 years, range 18-92 years) with proven chronic pancreatitis were enrolled. The SF-36 questionnaire was used for assessing the health-related quality of life. RESULTS: The z-scores of the eight domains of the patients with chronic pancreatitis were significantly negative indicating an overall impairment of the quality of life when compared to the Italian normative sample. Pancreatic pain was the unique clinical variable able to significantly impair all eight domains of the SF-36, while Wirsung dilation and diabetes were negatively related to some physical and mental domains. The body mass index was the unique variable positively related with some SF-36 domains. CONCLUSIONS: Pain may be considered the most important factor affecting the quality of life of chronic pancreatitis patients; moreover, alimentary and metabolic factors deserve more attention in improving the quality of life of these subjects.

Pancreatic hyperenzymaemia and hypertransaminasaemia in healthy subjects. Report of three cases.

Three healthy subjects, two from Italy and one from the United States, showing a chronic increase in serum pancreatic enzymes and transaminases are described. The enzyme elevations reached very high levels but were not constant; rather, they fluctuated and sometimes returned to normal. Furthermore, tests for non-hepatic diseases that can be accompanied by an increase in serum transaminases, such as coeliac disease, were normal. The intervals between the first finding of the pancreatic hyperenzymaemia and the hypertransaminasaemia and this study ranged from 2 to 6 years (mean 4.3 years), during which the three subjects remained healthy, with no clinical, laboratory or imaging evidence of disease. These data support the conclusion that these increases in enzymes are benign; however, monitoring of these three subjects is already underway. Awareness of this anomaly is important, both to relieve the distress of the persons involved, as well as to avoid the numerous, sometimes invasive, complex and expensive examinations that might otherwise be unnecessarily performed.

A meal stimulation test in the diagnosis of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

BACKGROUND: The diagnostic value of the determination of the serum pancreatic polypeptide (PP) and gastrin concentrations after a standard meal for early diagnosis of patients with multiple endocrine neoplasia type 1 (MEN 1) is controversial. The aim of this study was to clarify this issue. Thirteen patients with MEN 1, seven healthy family members, and eight healthy controls were studied. Plasma PP and serum gastrin were measured before and after the ingestion of a standardized meal. The meal caused a statistically significant (p < 0.05) increase of both PP and gastrin in all three groups studied. Concerning PP, no statistically significant difference was observed between patients and controls. In family members, the values were significantly (p < 0.05) lower than in the other two groups. On the whole, no significant differences in gastrin levels were noted between patients and controls; in family members, the values were significantly (p < 0.05) lower than in patients. All patients who had abnormally high postprandial values of PP and gastrin also had abnormally high basal values of these two peptides. The determination of serum PP and gastrin levels after a meal stimulation test in patients with MEN 1 adds no information about the presence of pancreatic endocrine tumors over that provided by basal values of the two peptides.

Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?

Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7-24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.

Diagnostic value of plasma chromogranin A in neuroendocrine tumours.

AIM: The aim of this study was to assess the value of plasma chromogranin A (CgA), a protein produced by neuroendocrine cells, in the diagnosis of neuroendocrine tumours. METHODS: Eighty subjects with neuroendocrine tumours were studied. Thirty-four had carcinoids, 21 nonfunctioning endocrine pancreatic tumours, 17 multiple endocrine neoplasia type 1 (MEN 1) (six of these also had gastrinomas), and eight had functioning pancreatic tumours (four gastrinomas, two glucagonomas, two somatostatinomas). Twenty-eight healthy subjects were studied as controls. A fasting plasma sample was obtained from each subject, and CgA plasma levels were measured by the ELISA method using a kit (Dako A/S, Denmark). RESULTS: In control subjects, plasma CgA values were below 5 U/l. Among the patients, 20 of the 34 with carcinoid tumours, 12 of the 21 with nonfunctioning pancreatic tumours, nine of the 17 with MEN 1 (including the six with gastrinomas), and the four gastrinomas of the eight functioning pancreatic tumours, i.e. overall, 45 of the 80 patients (56.3%) had abnormally high CgA values (22-961 U/l). Most of the patients with elevated CgA values, except nine of the 10 with gastrinomas, had multiple liver metastasis. CONCLUSIONS: The results show that the diagnostic value of plasma CgA in neuroendocrine tumours is relatively low; it may be of some interest only in patients with advanced disease and liver metastasis. Gastrinoma seems to be an exception, because in this tumour high CgA values are generally found even in the absence of liver metastasis.

Multivisceral eosinophilic fibrosis: a new clinical presentation.

We describe a patient who was referred to us with the diagnosis of pancreatic cancer but who had eosinophilic fibrosis of the pancreas and other organs, including the sub-mandibular salivary glands, retro-orbital tissue, liver, kidneys, and surrounding the abdominal aorta. He had no pain or other symptoms. After treatment with methylprednisolone, all lesions disappeared and now he seems to be cured of this apparently immune-mediated disorder. To our knowledge, involvement of all these particular organs by eosinophilic fibrosis in the absence of symptoms has never before been described.

Behaviour of serum pancreatic enzymes in chronic pancreatitis.

AIM: To establish whether serum pancreatic enzyme determination is useful in the identification of patients with chronic pancreatitis and in revealing the presence of exocrine pancreatic insufficiency PATIENTS AND METHODS: A total of 50 patients with chronic pancreatitis were included in the investigation: 19 were studied during a painful attack of the disease and 31 were observed during clinical remission of the disease and underwent a secretin-caerulein test; 21 of the 31 patients had severe pancreatic insufficiency. Thirty patients with non-pancreatic digestive diseases were also studied. Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase- were determined in all patients. RESULTS: Serum levels of the 5 enzymes studied were significantly higher in patients with pancreatic pain than in those studied during a clinical remission of the disease, and in those with non-pancreatic digestive diseases. In patients with chronic pancreatitis studied during clinical remission of the disease serum levels of pancreatic isoamylase and trypsinogen were significantly lower than in those patients with non-pancreatic digestive diseases. Considering only low serum concentrations of the five enzymes studied in diagnosing chronic pancreatitis, trypsinogen showed a sensitivity of 28%, specificity of 100%, a predictive value of a positive test of 100% and a predictive value of a negative test of 96.4%. In the 21 patients with severe pancreatic insufficiency, abnormally low serum concentrations of trypsinogen were found in 12 patients (57%), of lipase and elastase-1 in 6 (29%), of pancreatic isoamylase in 5 (24%), and of amylase in 3 (14%). CONCLUSIONS: Serum pancreatic enzymes can not be considered a useful tool to identify patients with pancreatic insufficiency. However, of the five enzymes studied, serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis.

Medical treatment of chronic pancreatitis.

The medical treatment has an important role in patients with chronic pancreatitis. Pain is the most frequent symptom, at least in the initial phases of the disease. In about 60% of patients it can be successfully treated by medical therapy; in the remaining 40% it requires surgery. Malabsorption of fat and protein and diabetes usually appear in the advanced stages of the disease. The treatment of these complications is based on the administration of pancreatic extracts and insulin. There are several types of pancreatic extracts; the most useful are those with high lipase content and high lipase-protease ratio. Moreover, they should be protected against gastric acid and should have a gastric emptying simultaneously with chyme, with a rapid liberation of enzymes into the duodenum. The treatment of diabetes usually requires low-moderate doses of insulin. Diabetic ketoacidosis is rare, while microvascular changes have the same frequency as in type 1 diabetes.

Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR.

BACKGROUND: Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days. AIM: To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours. METHODS: A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months). RESULTS: In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed. CONCLUSIONS: Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.

Familial pancreatic hyperenzymemia.

I recently described a new form of pancreatic hyperenzymemia in healthy subjects in the absence of any pancreatic disease. The aim of this study was to determine whether this pancreatic hyperenzymemia has a familial distribution. From January 1996 to January 1999, 25 subjects with chronic nonpathological pancreatic hyperenzymemia were seen, in 23 of whom it was possible to investigate family members. A total of 102 subjects was studied. In addition to clinical history, physical examination and routine blood analysis, serum amylase, pancreatic isoamylase, lipase, and amylasuria were determined. Abdominal ultrasonography was also performed. Seven of the 23 families studied were found to have more than one member with pancreatic hyperenzymemia. In all, 19 persons (eight female and 11 male) were found to have this trait (mean age, 32.7 years; range, 3-84). The increase in enzyme concentration over the upper normal limit was in the range of 1.3- to 5.2-fold for amylase, 1.4- to 8.6-fold for pancreatic isoamylase, and 1.6- to 18.0-fold for lipase. Amylasuria was also increased. Clinically, no subject had symptoms or signs of pancreatic or other disease. Abdominal ultrasonography was normal in all of them. The results of this study show that pancreatic hyperenzymemia in healthy subjects may present with a familial distribution. The underlying defect in this disorder is not known. Although it is a benign condition, awareness of it is important to avoid unnecessary concern, examinations, and expenditure.

Diabetes and the risk of pancreatic cancer.

AIMS: Diabetes occurs more frequently in patients with pancreatic cancer than in the general population, and it has repeatedly been claimed that it is a risk factor for this tumor. However in most of the studies on this subject the duration of diabetes before the diagnosis of pancreatic cancer was not ascertained. In an attempt to clarify the cause of the association between these two pathologic conditions and to determine whether diabetes is a risk factor for pancreatic cancer we recently studied this association in a large number of patients with pancreatic cancer. METHODS: A total of 720 patients with newly diagnosed pancreatic cancer (415 men and 305 women; mean age 62.6 years, range 22 to 79 years) and 720 controls matched for sex, age, social class, and geographic region, were enrolled in the study. All subjects were interviewed personally and in detail about their clinical history. The diagnosis of diabetes was based on criteria recommended by the American Diabetes Association. RESULTS: One hundred sixty-four patients with pancreatic cancer (22.8%) and 60 controls (8.3%) had diabetes. In the majority of the patients with pancreatic cancer (56.1%), diabetes was diagnosed either concomitantly with the cancer (in 40.2%), or within two years before the diagnosis of cancer (in 15.9%). The association between the two conditions was significant (odds ratio, 3.04; 95% confidence interval, 2.21 to 4.17). However, when only patients with diabetes of three or more years' duration were considered, the association was no longer significant (odds ratio, 1.43; 95% confidence interval, 0.98 to 2.07). All the patients with pancreatic cancer whose diabetes had been diagnosed before the cancer had non-insulin-dependent diabetes; all but one of the control patients with diabetes had the non-insulin-dependent form of the disease. CONCLUSIONS: Diabetes in patients with pancreatic cancer is frequently of recent onset and is presumably caused by the tumor. Diabetes is not a risk factor for pancreatic cancer.

Risk of pancreatic and periampullary cancer following cholecystectomy.

AIMS: Cholecystectomy has been reported by several investigators to increase the risk of pancreatic cancer. The trophic effect on the gland by increased release of cholecystokinin following cholecystectomy and perturbation of the neurohormonal pancreatic regulation, have been suggested as possible contributing factors. However, while several investigators found that this surgical procedure increases the risk, others have not. In an attempt to clarify whether or not patients who have undergone cholecystectomy are at increased risk for developing pancreatic cancer, we evaluated the frequency with which cholelithiasis and this surgical procedure were present in a large number of patients with pancreatic cancer. METHODS: A total of 720 patients with newly diagnosed pancreatic cancer (415 men and 305 women; mean age 62.6 years, range 22 to 79 years) and 720 controls matched for sex, age, social class, and geographic region, were enrolled in the study. All subjects were interviewed personally and in detail about their clinical history. RESULTS: Cholelithiasis was present in 126 patients with pancreatic cancer (17.5%) and in 95 controls (13.2%), constituting a statistically significant association (odds ratio, 1.39; 95% confidence interval, 1.04 to 1.86). However, considering only the patients and controls in whom the diagnosis of cholelithiasis was made for more than one year before cancer diagnosis or interview, the association was no longer significant (odds ratio, 1.04; 95% confidence interval, 0.75 to 1.44). Cholecystectomy had been performed in 93 patients with pancreatic cancer (12.9%) and in 71 controls (9.9%). When all subjects were considered, the odds ratio was mildly, although not significantly, increased (odds ratio, 1.35; 95% confidence interval, 0.97 to 1.87). When only subjects who underwent cholecystectomy one year or more before the cancer diagnosis or interview were considered, the odds ratio fell to unity (odds ratio, 1.00; 95% confidence interval, 0.70 to 1.43). CONCLUSION: This study, one of the largest on this topic, clearly shows that there is no evidence for an association between cholelithiasis, cholecystectomy, and pancreatic cancer.